EPFL - ISIC - LSPN Hydrogen-Mediated C-C Bond Formation History and selected examples The Research of Prof. Michael Krische (University of Texas at Austin) LSPN Group Seminar Mathias Mamboury
Table of contents 1) Introduction 2) Homogeneous catalytic hydrogenation H 2 History and hydroformylation 3) Rhodium catalysis Aldol couplings 4) Iridium catalysis Allylation / crotylation 5) Ruthenium catalysis Crotylation & hydroacylation 6) Conclusion 2
1) Introduction 2) Homogeneous catalytic hydrogenation 3) Rhodium catalysis 4) Iridium catalysis 5) Ruthenium catalysis 6) Conclusion 3
1) Introduction From the 1st homogeneous catalytic hydrogenation by Calvin in 1938 Trans. Faraday Soc. 1938, 34, 1181-1191 to highly atom economical transformations of great interest : J. Am. Chem. Soc. 2011, 133, 12795-12800 Without H 2! Science 2012, 336, 324-327 4
1) Introduction Professor Michael J. Krische : 1986-1989 : B.S. Chemistry / University of California at Berkeley / Prof. H. Rapoport 1990-1996 : Ph.D. Chemistry / Stanford University / Prof. B. M. Trost 1997-1999 : NIH Post-Doc. / Université Louis Pasteur / Prof. J.-M. Lehn Since 1999 : Professor at the University of Texas at Austin 2002 1st H 2 -mediated C-C coupling Early years : Rhodium Currently : Iridium & Ruthenium Krische Ir-Catalyst Commercially available: Aldrich CPR : 92 CHF / 100 mg 2016 > 90 papers published in this field 5
1) Introduction 2) Homogeneous catalytic hydrogenation 3) Rhodium catalysis 4) Iridium catalysis 5) Ruthenium catalysis 6) Conclusion 6
2) Homogeneous catalytic hydrogenation The History of homogeneous catalytic hydrogenation : 1938, Calvin : 1st homogeneous catalytic hydrogenation Trans. Faraday Soc. 1938, 34, 1181-1191 1961, Halpern : 1st hydrogenation of activated alkenes J. Am. Chem. Soc. 1981, 63, 753-754 1966, Wilkinson : 1st hydrogenation of unactivated alkenes and alkynes J. Chem. Soc. A 1966, 1711-1732 7
2) Homogeneous catalytic hydrogenation The History of homogeneous catalytic hydrogenation : 1971, Kagan : 1st enantioselective hydrogenation of alkenes J. Chem. Soc. D 1971, 481 1977, Crabtree : highly efficient Ir-catalyst for the hydrogenation of alkenes J. Organomet. Chem. 1977, 135, 395-403 1987, Noyori : Ru-catalyst for the hydrogenation of alkenes J. Org. Chem. 1987, 52, 3174-3176 8
2) Homogeneous catalytic hydrogenation The History of homogeneous catalytic hydrogenation : 1995, Noyori : 1st efficient enantioselective hydrogenation of aromatic ketones J. Am. Chem. Soc. 1995, 117, 2675-2676 Ater 2000 : Early transition metals. Chemo-, diastereo- and enantioselectivity. Ability to reduce almost any unsaturated functional group. Applications for energy and environment? etc. Late 1960 : homogeneous transfer hydrogenation Chem. Rev. 1974, 74, 567-580 (refs 9-13) 9
2) Homogeneous catalytic hydrogenation An intruiging and inspiring reaction left aside : 1938, Roelen : Hydroformylation DE Patent 849 548 (1938) «Hydroformylation is one of the most important industrial processes based on homogeneous catalysis». Acc. Chem. Res. 2003, 36, 264 275 Another point of view : C-C bond formation with H 2 as terminal reductant! Powerfull concept : - Atom economic - Versatile if applicable with any carbonyl group other than CO any alkene or alkyne 10
1) Introduction 2) Homogeneous catalytic hydrogenation 3) Rhodium catalysis 4) Iridium catalysis 5) Ruthenium catalysis 6) Conclusion 11
3) Rhodium-catalysis Hydrogenation with the Wilkinson catalyst : How could we form a C-C bond? Strategy : Trap a carbonyl compound with one of the intermediates (or similar). Challenge : Generate a Rh-intermediate that is nucleophilic enough to attack the carbonyl. Proposal : Rh-enolate! J. Chem. Soc. A 1968, 2665-2671 12
3) Rhodium-catalysis 1st (almost) H 2 -mediated C-C coupling beyond hydroformylation : aldol coupling Postulated intermediate : J. Am. Chem. Soc. 2002, 124, 15156-15157 Org. Lett. 2003, 5, 1143-1146 Org. Lett. 2004, 6, 691-694 Acc. Chem. Res. 2004, 37, 653-661 13
3) Rhodium-catalysis Observation during the optimization : Mechanism : Org. Lett. 2003, 5, 1143-1146 Acc. Chem. Res. 2004, 37, 653-661 Neutral Rh(I) homolytic cleavage of H 2 1,4-reduction Cationic Rh(I) + base heterolytic cleavage of H 2 traping 14
3) Rhodium-catalysis Intermolecular aldol coupling and diastereoselectivity : Ligand Yield d.r. PPh 3 31% 3:1 (2-furyl)Ph 2 P 24% 6:1 (2-furyl) 2 PhP 52% 15:1 (2-furyl) 3 P 74% 19:1 (2-furyl) 3 P = Simplest explanation, among others : The rhodium center is more Lewis acidic, rendering the Zimmermann-Traxler transition state more «tight» : Org. Lett. 2006, 8, 519-522 Org. Lett. 2006, 8, 5657-5660 15
3) Rhodium-catalysis Enantioselective aldol coupling (2008) : Design of the ligand : Scope : Limitations : J. Am. Chem. Soc. 2008, 130, 2746-2747 Etc. 16
3) Rhodium-catalysis Summary : Rh-catalyzed aldol couplings are the first H 2 -mediated C-C couplings beyond hydroformylation : Atom economic Mild conditions Intra- and intermolecular High diastereoselectivities Enantioselective for MVK 17
3) Rhodium-catalysis Other transformations with rhodium : Postulated intermediates : J. Am. Chem. Soc. 2005, 127, 11269-11276 Org. Lett. 2006, 8, 3873-3876 Org. Lett. 2007, 89, 3745-3748 18
3) Rhodium-catalysis From rhodium to iridium : Major limitation : only works with conjugated alkynes Alternative : Stronger π-donor than Rh (relativistic effects) May react with higher lying non-conjugated LUMOs π-backbonding to alkyne may render the Ir-alkyne intermediate more nucleophilic* *J. Am. Chem. Soc. 2007, 129, 8432-8433 (note 9) J. Am. Chem. Soc. 2007, 129, 12644-12645 J. Am. Chem. Soc. 2007, 129, 280-281 19
1) Introduction 2) Homogeneous catalytic hydrogenation 3) Rhodium catalysis 4) Iridium catalysis 5) Ruthenium catalysis 6) Conclusion 20
4) Iridium-catalysis Enantioselective carbonyl allylation : Transfer hydrogenation (= TH) with i-proh as hydrogen donor! Only byproducts: One step further : Acetone Acetic acid Hydrogen auto-transfer! Only byproduct: Acetic acid J. Am. Chem. Soc. 2008, 130, 6340-6341 J. Am. Chem. Soc. 2008, 130, 14891-14899 Highly atom economic! 21
4) Iridium-catalysis Enantioselective carbonyl allylation : Optimization : Scope : Benzoic acid Yield o-no 2 BzOH 39% m-no 2 BzOH 81% p-no 2 BzOH 49 J. Am. Chem. Soc. 2008, 130, 6340-6341 J. Am. Chem. Soc. 2008, 130, 14891-14899 Etc. 22
4) Iridium-catalysis Enantioselective carbonyl allylation : Mechanism : J. Am. Chem. Soc. 2008, 130, 14891-14899 J. Am. Chem. Soc. 2009, 131, 2514-2520 This pre-formed catalyst shows higher performance (% and e.e.) than the in-situ prepared catalyst! 23
4) Iridium-catalysis Related reactions : crotylation & alkoxyallylation Crotylation : Krische Ir-Catalyst Commercially available: Aldrich CPR : 92 CHF / 100 mg Chem. Commun. 2011, 47, 10028-10030 Alkoxyallylation : J. Am. Chem. Soc. 2009, 131, 2514-2520 J. Am. Chem. Soc. 2010, 132, 1760-1761 24
4) Iridium-catalysis Addition to diols : J. Am. Chem. Soc. 2010, 132, 1760-1761 25
4) Iridium-catalysis Summary : Ir-catalyzed allylations (and similar transformations) are among the first TH-mediated C-C couplings : Atom economic No H 2 gas Simple conditions Diastereo- and enantioselectivity Bypasses redox manipulations 26
1) Introduction 2) Homogeneous catalytic hydrogenation 3) Rhodium catalysis 4) Iridium catalysis 5) Ruthenium catalysis 6) Conclusion 27
5) Ruthenium-catalysis Crotylation : 1st C-C bond formation with ruthenium under TH All attempts using iridium failed for non-cyclic dienes! Fully atom economic! Observation: Suppressed by addition of a ligand to block the coordination sites required for β hydride elimination. Hydroacylation : No additionnal ligand! J. Am. Chem. Soc. 2008, 130, 6338-6339 J. Am. Chem. Soc. 2008, 130, 14120-14122 28
5) Ruthenium-catalysis Crotylation and hydroacylation : These 2 reactions also work with All oxidation levels of substrate and product are accessible! J. Am. Chem. Soc. 2008, 130, 6338-6339 J. Am. Chem. Soc. 2008, 130, 14120-14122 No redox manipulations of starting materials et products required! 29
5) Ruthenium-catalysis Enantioselective crotylation : Inversion of diastereoselectivity : Science 2012, 336, 324-327 J. Am. Chem. Soc. 2012, 134, 20628-20631 30
5) Ruthenium-catalysis Enantioselective crotylation : Mechanism : Science 2012, 336, 324-327 31
5) Ruthenium-catalysis Summary : Ru-catalyzed crotylations are among the first TH-mediated C-C couplings : Fullly atom economic Bypasses redox manipulations No H 2 gas Simple conditions Diastereo- and enantioselectivity 32
1) Introduction 2) Homogeneous catalytic hydrogenation 3) Rhodium catalysis 4) Iridium catalysis 5) Ruthenium catalysis 6) Conclusion 33
6) Conclusion A long way : 1938 : Trans. Faraday Soc. 1938, 34, 1181-1191 Years 2000 : Beautifull concepts Complementary metals Modern chemistry : Simple and cheap starting materials Valuable products Diastereo- and enantioselectivity Atom economic / green «Because organic molecules are compounds composed of C and H, the formation of C-C bonds under (transfer) hydrogenation conditions is a natural end point in the evolution of strategies for organic synthesis». Science 2012, 336, 324-327 34
6) Conclusion Thank you for your attention! Questions / discussions? This presentation is not a complete review on H 2 -mediated C-C bond formation! See research.cm.utexas.edu/mkrische for the full list of publications! 35